PLS Pharma Logistics – Published Case study on Good Distribution Practice and the Pharmaceutical Supply Chain.

See links below for more details:

Global Logistics and Supply Chain Management – Paperback (8 April 2008) by John Mangan, Chandra Lalwani, and Tim Butcher

Links: Read Case Study Here

For more information on this case study please contact us or telephone + 353 1 20 200 20.

In the pharmaceutical industry, good distribution is not just a case of guaranteeing that a patient’s supply of medicine is made available on time when needed, it is a case of ensuring that the entire supply chain and distribution network is focused on supplying a quality product that complies at every point with regulatory requirements and is fit for use when it reaches the patient. Any failings within the pharmaceutical supply chain can seriously compromise the quality of the product and hence patient safety.

In this context, the supply chain extends well beyond the vehicles used to take bulk pharmaceutical (such as APIs) and medical components to the manufacturing facility and finished products from the manufacturing facility to distributors/wholesalers. It also must ensure compliant delivery to hospitals, pharmacies and even supermarkets where patients receive their medicines. We all, as patients, would like to know that the excellent quality under which medicines are made in the manufacturing facility extends all along the legitimate supply chain and we and our families are always safe.

Good distribution practice (GDP) is about much more than just the distrib ution of products. The MHRA (the UK authority) recently defined GDP as “the sum of all of the processes and activities designed and implemented to ensure that the quality of medicines is maintained throughout the distribution chain from manufacturer to patient, ensuring compliance with regulatory requirements at all relevant stages. It includes the storage and transportation of APIs, other ingredients and packaging components used in the production of the medicines.”

In effect, GDP extends to sourcing materials from approved suppliers and continues through manufacturing (under GMP) and on to delivery of the product to the final customer or patient.

The supply chain is becoming more complex and global, raising serious practical questions about where the supply chain starts and ends, and precisely where control must be focused to guarantee quality all the way from ingredients to the final medicine. The more global and complex the distribution network, the more difficult it is to ensure that goods follow approved routes, are transported by approved and trained delivery drivers, and that records are properly maintained and quality is assured at every point along the pharmaceutical supply chain.

The global growth of counterfeiting, not only of finished products but also of APIs, is a major issue for the industry. The implementation of GDP is essential for keeping counterfeits out of the legitimate supply chain/distribution network, and lapses in GDP can leave any pharmaceutical supply chain vulnerable to counterfeits.

Hence, good distribution practice remains an essential aspect of compliance for all pharmaceutical products as raw material and products are transported and delivered on a global and local basis.

The pharmaceutical industry in Ireland

Ireland is one of the leading international locations for the life science industry, which spans pharmaceuticals, chemicals, diagnostics, medical devices and biotechnology. It generates over 50% of our exports, making Ireland the largest net exporter of medicines globally. Ireland is home to 13 of the top 15 companies in the world and manufactures nine of the world‘s top 15 medicines. In 2008, there were over 24,500 people employed in the sector producing exports of over €44 billion.

Globally, the sector has been expanding by 5-6% per annum since the turn of the decade, and last year it recorded global sales of $745bn. By comparison, exports of life sciences products from Ireland have more than doubled in the same time frame and now account for 9% of global sales.

Therefore, it is essential that the heart of the Irish economy keeps beating by ensuring a consistent, efficient and safe supply chain for the pharmaceutical industry, which will only bring benefits to Ireland in the form of more investment, more businesses and more employment

Good distribution practice

The World Health Organisation defines GDP as “that part of quality assurance that ensures that the quality of pharmaceutical products is maintained by means of adequate control of the numerous activities which occur during the distribution process as well as providing a tool to secure the distribution system from counterfeits, unapproved, illegally imported, stolen counterfeit, sub-standard, adulterated, and/or misbranded pharmaceutical products”. The critical need to establish controls at all points of the supply chain is an increasing challenge for all pharmaceutical companies and their partners in handling and transporting medicines globally.

As previously stated, the GMP manufacturer licence holder is fully responsible to ensure that any third party contractor involved in transportation and storage is fully compliant with the terms of their licence.

By dealing with an accredited GDP Passport service provider, the manufacturer is ensuring that only bona fide operators are transporting, handling and storing their products in accordance with the regulator’s guidelines and ultimately helping to ensure patient safety.

A matter of increasing concern internationally

Counterfeit, unapproved, illegally imported, stolen counterfeit, adulterated, misbranded. These are all words which are becoming an increasing concern for governments, regulators and international health organisations. The rapid growth of counterfeit medicines that can be potentially lethal for the final consumer has seen a strong international reaction demanding more controls and security in the supply chain of pharmaceutical products to ensure that the final consumer receives the products safely.

At the beginning of 2008, the World Health Organisation (WHO) published a document titled Good Distribution Practices (GDP) for Pharmaceutical Products currently being discussed. This guidance is the counterpart of the document Good Trade and Distribution Practices for Pharmaceutical Starting Material, which was published by the WHO in 2003.

At a European level, the EU published its Guidelines of Good Distribution Practice of Medicine Products for Human Use (94/063/3) dating back to 1992.

The International Air Transport Association (IATA) introduced a new set of regulations for airlines and ground handlers on July 1st, 2009 to counter a pharmaceutical industry report that suggested that 50% of temperature deviations occur when the consignments are in the hands of the airlines and their facilities.

Within the GDP principles from the WHO it is stated that “the principles of GDP should be included in national legislation and guidelines for the distribution of pharmaceuticals products… as a means of establishing minimum standards”. This shows us the importance that GDP is receiving and also gives a hint of the way legislators will follow.

GDP Passport from the IEA

The Irish Exporters Association (IEA), assisting the Irish export sector to improve its competitiveness for over 58 years, saw the need to keep Ireland as a world leader in the pharmaceutical sector and the importance that this sector has for the Irish economy. Born from the need for all stakeholders involved in the life science industry to ensure supply chain integrity and final consumer safety, the IEA, in close collaboration with the Irish Medicine Board (IMB), drew up the Good Distribution Practices Passport Scheme, with the main objective of helping to ensure that Ireland remains the preferred location for life sciences companies to develop, manufacture and distribute their products internationally.

The GDP Passport from the IEA is the first of its kind and ensures compliance and safety throughout the whole supply chain. Manufacturers then can ensure that their products are transported, stored and handled according the GMP and GDP regulations and guidelines by dealing with GDP Passport holders.

The code is focused on providing training courses to all levels of personnel involved in the supply chain. The key to success is the full suite of standardised and certified training, which is to be undertaken by all those engaged either directly by the manufacturer or indirectly by the service provider in distribution activities, as stated in WHO Good Distribution Practices for Pharmaceutical Products, section 7.1.

The training needed to become a GDP Passport holder are outlined below:

1) The appointment of a GDP Champion, who must have completed an intensive three-day GDP training module;

2) All relevant operational staff must complete the one-day GDP Introduction Programme;

3) All drivers involved in transportation and handling of pharmaceutical products must complete a two-Hour Driver Training course.

The industry has also recognised the need for a compliant supply chain for pharmaceutical products, and the GDP Passport was enthusiastically welcomed when it was launched in October 2009 by Patrick O’Mahony, CEO of the Irish Medicine Board.

Indeed, several companies, both indigenous and international, have already signed up to the GDP Passport to undergo the training required, and the IEA has already awarded two companies with the GDP Passport.

In 2010, a further group of companies will have met the requirements and will be awarded with the GDP Passport, making Ireland the leader in pharmaceutical supply chain compliance.

Picture shows Mr. Pat O’Mahony CEO Irish Medicines Board (IMB)

Guest of Honour & Keynote Speaker at the Formal Launch of Irish

Exporters Association Life Science GDP Code of Practice & GDP

Passport Scheme for Supply Chain Service Providers. Also in the picture

from left to right Ciaran Brady, Managing Director, PLS Pharma Logistics

(approved Training Providers for the GDP Passport) , John Whelan CEO,

Irish Exporters Association, Pat O’Loughlin Director Life Science Ireland,

Managing Partner O’Loughlin Partnership & Mike Bennett Chairperson

Leinster IEA Life Science Ireland ( Director Logistics Pfizer

Grangecastle Biopharmaceutical Site).

Business opportunity

The GDP Passport provides to the industry quality and compliance throughout the whole supply chain, bringing Ireland to the next level of security, quality and compliance in the supply chain for the pharmaceutical and healthcare industry.

In the current economic climate, a key milestone must be to ensure that Irish companies make the most of the competitive advantages they currently have, and the life sciences industry is, without any doubt, a stronghold for the Irish economy. Thus it is vital that this advantage is kept and improved so Ireland can become the first choice for life sciences companies when it comes to establishing new manufacture centres from which to distribute worldwide.

To sum up, the GDP Passport benefits not just manufacturing and logistics companies, but the whole Irish economy.

Raul Molina is manager of Life Sciences Ireland, part of the Irish Exporters Association. Email: raulmolina@irishexporters.org , Tel: +353 (0)1 661 21 82, www.irishexporters.ie

Ciaran Brady is managing director of PLS Pharma Logistics. Email: info@plspharmalogistics.com , Tel: +353 (0)1 2020020. http://www.plspharmalogistics.com

With pharmaceuticals, good distribution is not just a case of guaranteeing that a patient’s supply of medicine is made available as and when it is needed – although that is, of course, essential. Rather it is a case of ensuring that the entire supply chain or distribution network is focused on supplying a quality product that complies at every point with regulatory requirements and is fit for use at the time that it reaches the patient. Any failings or faults within the chain, even seemingly innocuous failings, can seriously compromise the quality of the product and hence the safety of patients.
In this context, the supply chain extends well beyond the vehicles used to take the product from manufacturing facility to patient. It includes all the interconnected company processes, procedures and distribution points from sourcing of ingredients, through receipt of goods, order taking, picking and invoicing, warehouse maintenance and staff training.
Good Distribution Practice (GDP) is about much more than just the distribution of products. The MHRA recently defined GDP as ‘the sum of all of the processes and activities designed and implemented to ensure that the quality of medicines is maintained throughout the distribution chain from manufacturer to patient, ensuring compliance with regulatory requirements at all relevant stages. It includes the storage and transportation of APIs, other ingredients and packaging components used in the production of the medicines.’
In effect, GDP extends to sourcing materials from approved suppliers and continues through manufacturing (under GMP) and on to delivery of the product to the final customer or patient.

This is a fairly simple observation that disguises a truly challenging picture. The supply chain is becoming more complex and global, raising serious practical questions about where the supply chain starts and ends, and precisely where control must be focused to guarantee quality all the way from ingredients to the final medicine. The more global and complex the distribution network, the more difficult it is to ensure that goods follow approved routes and that delays are avoided, that records are properly maintained and that quality is assured at every point.

The observation that climate change appears to be leading to some violent fluctuations in temperature and humidity in different locations around the world also needs to be factored into the equation. This raises genuine concerns about what happens to products as they wait to be loaded onto trucks, trains, ships or planes. One also has to take account of the risk that product might sit in the back of a truck that is caught in a traffic jam or has broken down.

The global growth of counterfeiting not only of finished product but also of APIs is also an issue. The implementation of GDP is essential for keeping counterfeits out of the legitimate supply chain/distribution network, and lapses in GDP can leave any pharmaceutical supply chain vulnerable to counterfeits.
Global warming
The suggestion that global warming has an impact on GDP is no idle claim. Both the FDA and MHRA single out temperature as a critical control parameter for ensuring pharmaceutical quality.
FDA CFR 211.142 states the need to ensure ‘Storage of drug products under appropriate conditions of temperature, humidity and light so that the identity, strength, quality and purity of the drug products are not affected.’ These sentiments are also reflected in many other guidance documents (see table 1).

John Taylor, of the MHRA, has noted publicly that: ‘The regulator expects companies to take the view that control and monitoring of the temperate chain is as important as the cold chain.’ He also observes that: ‘Each shipment between countries and within countries of large geographical area should be treated as unique in terms of the range of temperatures the goods may experience.’ This recognises the huge temperature variations that ingredients and medicines may experience on any given journey and in any given location.

Despite this emphasis, poor temperature control during storage and transportation is a regular cause of failure during inspections. According to MHRA, 32% of all critical and major deficiencies are concerned with control and monitoring of storage and transportation. The insurance industry shares this perspective. John Perera, a risk management consultant with Royal & Sun Alliance, said: ‘I have seen many cases where simple acts of ignorance have meant that millions of pounds of temperature-sensitive pharmaceuticals have had to be destroyed.

‘Products have been stored in warehouses at the wrong temperature, or drivers have failed to set the right temperature within their containers. Simple, easily avoidable errors can put patients at risk as well as costing millions of pounds in damages. It is often down to the ignorance or lack of knowledge of one person, but there are also examples of a systematic failure from some manufacturers to set specifications and a systematic failure from distributors to adhere to them.’
Keeping out counterfeits

One of the biggest challenges for the pharmaceutical industry, and one of the main reasons why GDP is so important, is the increase of counterfeiting on a global basis.
Various measures of the scale of the counterfeit problem have been published, and there were 10 recalls in the UK between 2004-7 in which counterfeits have reached the patient level.

The US-based Centre for Medicines in the Public Interest has predicted that counterfeit drug sales will reach US $75bn (b55bn) globally in 2010, which would represent a 90% increase on 2005. The WHO suggests that counterfeits account for around 1% of sales in developed countries to more than 10% in developing countries, and medicines purchased over the Internet from sites that conceal their physical address are counterfeit in at least 50% of cases.

GDP is a minimum requirement in helping to stem the flow of counterfeit products into legitimate pharmaceutical supply/distribution channels. The practice of parallel distribution, and the complex interfaces between manufacturers, distributors and repackagers, especially around withdrawal of product and subsequent approved disposal, are all areas of potential weakness that counterfeiters are only too willing to exploit. There is also a substantial risk associated with returns, and specific training is required to help staff deal effectively with them.

Indeed, the need for all stakeholders in the pharmaceutical industry to work in partnership to ensure supply chain integrity and that only bona fide suppliers and customers are allowed to supply and sell is a must if we are to ensure patient safety at all times.

As the recently published Orange Guide notes in its introduction, ‘The great majority of reported defective medicinal products has resulted from human error or carelessness, not from failures in technology.’
From this it is apparent that individuals within companies must do everything expected of them to meet the requirements of GMP and GDP; by implication, they must first understand what those requirements are and where their own activities come under the remit of GDP and/or GMP.

Training is therefore an essential pre-requisite to the implementation of GDP, and that message does appear to be getting through. RSSL Pharma Training is one organisation that runs GDP courses and according to training manager Lyndsey Wright, uptake has increased dramatically in the past year.

‘The distribution network has sometimes been seen as something external to the production of pharmaceuticals. Now the industry realises that there is no point in exercising fine control over every aspect of production if there is no equivalent control of the product once it leaves the premises. That is not to say that no-one recognised this before, but there have been shortfalls in how the responsibility for product safety was passed on through the supply chain/distribution network and how it was enforced.’

Key components
There are several key components to getting GDP right, with training being just one aspect of the wider requirement for personnel to be adequately managed, motivated and resourced.
Manufacturers, wholesalers and distributors need also to consider and address their overall quality systems, documentation, premises (especially warehousing) and equipment, deliveries to customers (transportation and supply chain), returns, recall procedures and self inspections.
But there are other issues to address, such as the need to ensure that identification is not lost, that contamination is avoided and that products are secure at all times. It is one thing to be certain that the right product has been loaded properly into an appropriate vehicle with all the right documentation, but everything else that happens thereafter is beyond the direct control of the manufacturer.
Choosing the right supply chain/distribution network partners is not just a matter of choosing a distributor with the appropriate licence, because all the intermediaries that touch, move and handle the product ought to be considered too.
It is the unknown interventions that should concern us all. Selecting, establishing and maintaining the bona fides of all suppliers and customers is an essential but complicated aspect of GDP, especially in a global pharmaceutical market characterised by takeovers, mergers, increased regulator expectations and downward pressure on costs.
In summary, everyone involved in the business has a responsibility under GDP to protect patient safety. This responsibility extends from the technical department that deals with preparing the documents under which suppliers are contracted and under which shipping instructions are written, through to the IT manager responsible for record-keeping and data storage, because traceability is essential for successful recall.
While there are guidelines that can assist pharmaceutical manufacturers and distributors in achieving higher standards of compliance, training is a critical ingredient for success. It is people who manage the systems and the process, and who must ensure that GDP is adhered to.
Having well-trained and highly motivated staff will go a long way to ensuring that GDP is managed successfully throughout the supply chain/distribution network, and that pharmaceutical products are handled, transported and delivered with best-in-class GDP standards and full compliance.
Contacts:
Ciaran Brady
PLS Pharma Logistics
Dalkey Business Centre 17 Castle Street Dalkey Co. Dublin
Ireland T +353 1 20 200 20
info@plspharmalogistics.com

Lyndsey Wright
RSSL Pharma Training
Science & Technology Centre University of Reading Earley Gate, Whiteknights Road Reading, Berks
UK T +44 118 935 7344
pharma.training@rssl.com

It may be tempting to imagine that a manufacturer’s responsibility for a pharmaceutical product lies only within the ‘four walls’ of a manufacturing facility, but, of course, this has never been the case. Whether through legislation and guidelines or simple common sense, it is clear that at any point of the supply chain the integrity of all pharmaceutical products must be ensured and not compromised. In short, a manufacturer’s responsibility extends to sourcing materials from approved suppliers, continues through manufacturing under GMP, and on to delivering the product to the final customer or patient.

Hence, good distribution practice (GDP) remains an essential aspect of compliance for all pharmaceutical products as raw materials and products are transported and delivered on a global and local basis.

Moreover, as global supply chains are becoming more complex, and in the context of increasing commercial pressures, climate change and the global growth of counterfeiting, it is arguable that GDP has greater importance now than at any time since the first Orange Guide was published in 1971.

GDP

GDP is defined as “that part of quality assurance which ensures that products are consistently stored, transported and handled under suitable condition as required by the marketing authorization or product specification”. This definition could reasonably extend to include sourcing, receipt, storage and transportation — looking at the full supply chain that is necessary to make and sell pharmaceutical products. The critical need to establish controls at all points of the supply chain is an increasing challenge for all pharmaceutical companies and their partners in handling and transporting medicines globally.

The importance of GDP is elaborated on in the EU Guidance on Distribution Practice, which sets out a Principle as the basis for operating to GDP. The following summary of that principle does reliably reflect its observations: “The Community pharmaceutical industry operates at a high level of quality assurance … and this level of quality should be maintained throughout the distribution network so that authorized medicinal products are distributed to retail pharmacists and other persons entitled to sell medicinal products to the general public without any alteration of their properties.

“To maintain the quality of the products … Directive 92/25/EEC provides that wholesalers must comply with the principles and guidelines of GDP published by the Commission of the European Communities…”

Areas for concern

Recent information available from MHRA suggests there are many areas where the pharmaceutical sector is falling down regarding GDP. These include deficiencies such as general storage and transportation problems, documentation/procedural deficiencies, such as the lack of written or insufficient standard operating procedures (SOPs), and inadequate systems for dealing with returns; and personnel issues concerning duties of key staff — even the Responsible Person. There is no reason to suppose that the incidents highlighted in this extensive list are in any way restricted to the UK, and statistics from previous years highlight many of the same failings.¹ Worryingly, temperature control and monitoring is a recurring theme, and in the context of global warming the industry must address this issue. The Orange Guide makes specific reference to the requirement to ensure ‘proper conservation and distribution’ of medicines, and now contains recommendations on meeting these requirements.

Countering the counterfeiters

One of the biggest challenges for the pharmaceutical industry, and one of the main reasons why GDP is so important, is the increase of counterfeiting. The EC recently reported a fivefold increase in the seizure of counterfeit pharmaceutical items for 2006 compared with 2005.

The US-based Centre for Medicines in the Public Interest has predicted that counterfeit drug sales will reach $75 billion (€58 billion) globally in 2010. The WHO website suggests that counterfeits account for around 1% of sales in developed countries to in excess of 10% in developing countries, and medicines purchased via the internet from sites that conceal their physical address are counterfeit in more than 50% of cases.

GDP is a minimum requirement in helping to stem the flow of counterfeit products into legitimate distribution channels. The practice of parallel distribution, and the complex interfaces between manufacturers, distributors and repackagers — especially around withdrawal of product and subsequent disposal or reprocessing — are all areas of potential weakness that counterfeiters are only too willing to exploit. The need for all stakeholders in the pharmaceutical industry to work in partnership to ensure supply chain integrity and that only bona fide suppliers and customers are allowed to supply and sell is a must if we are to guarantee patient safety at all times.

Creating stronger links

Just as the manufacturer cannot disassociate itself from GDP, distributors cannot ignore their responsibilities under GMP. The preface of the new Orange Guide highlights the community requirements on distributors to adhere to the principles of GMP when repackaging and relabelling active substances used as starting materials.² It also notes a new requirement on distributors that import from other member states to notify the marketing authorization holder and the competent authority (within the import country) of the intention to import.³ Moreover, the competent authority now has powers to conduct unannounced inspections of any firms (including distributors) employed by the marketing authorization holder where there are grounds for suspecting non-compliance with GMP principles.

While it is the EU Amending Articles rather than the Orange Guide that have introduced these changes, there is no doubt that the new Orange Guide should make it clearer in everyone’s mind that these changes have come about. Both manufacturers and distributors need to fully understand their obligations under GMP and GDP, and to be aware where non-compliance could compromise a marketing authorization.

Getting it right

As the Orange Guide notes in its introduction: “The great majority of reported defective medicinal products has resulted from human error or carelessness, not from failures in technology”.

From this, it is apparent that individuals within companies must do everything expected of them to meet the requirements of GMP and GDP, and by implication, they must first understand what those requirements are, and where their own activities come under the remit of GDP and/or GMP.

Conclusion

GDP is as essential to the continued success of the pharmaceutical industry as GMP, and this fact is recognized in the new Orange Guide, which contains several new entries pertaining to the quality of pharmaceutical products under GDP.

Although the new guidelines are intended to assist pharmaceutical manufacturers and distributors in achieving higher standards of compliance, training is a critical ingredient for success. Having the correct and well-trained staff will ensure GDP (and GMP) is managed successfully along the supply chains, and that pharmaceutical products are handled, transported and delivered with best-in-class GDP standards and full compliance.

Ciaran Brady is managing director of PLS Pharma Logistics (Ireland). Lyndsey Wright is manager of the training centre at RSSL Pharma Training (UK).

References

1. J. Taylor et al., The Pharmaceutical Journal, 270, 129, 25 January 2003.

2. Articles 1(33)–(35) of Directive 2004/27/EC amending Articles 46, 46a and 47 of Directive 2001/83/EC.

3. Article 1(55) of Directive 2004/27/EC amending Article 76 of Directive 2001/83/EC.